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The VPS72-H2A.Z interaction blocking peptide is an experimental cell-permeable therapeutic agent designed to disrupt the binding between the histone chaperone VPS72 and the histone variant H2A.Z. VPS72 is a shared subunit of the SRCAP and TIP60 remodeling complexes and is responsible for the ATP-dependent deposition of H2A.Z-H2B dimers into regulatory chromatin. In lung adenocarcinoma (LUAD), this axis is frequently upregulated and supports oncogenic transcriptional programs, including MYC- and E2F-driven cell-cycle progression, metabolic adaptation, and immune evasion. By blocking the VPS72-H2A.Z interface, the peptide prevents the incorporation of H2A.Z into DNA, thereby inducing apoptosis and inhibiting the proliferation, migration, and invasion of cancer cells. This epigenetic modulator represents a novel strategy to overcome therapeutic resistance and plasticity in aggressive non-small cell lung cancer.
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